Ethyl chloroformate → (N-1-azabicyclo[2.2.2]oct-3-yl)-8-chloro-5-ethoxy-1,2,3,4-tetrahydroquinoline-6-carboxamide

HRID 2074010Notes

Reaction equation

HRID 2074010 reaction equation
Cl[C:2]([O:4][CH2:5][CH3:6])=O.C([C:10]1[C:11]([O:21]C)=[C:12]2[C:17](=[C:18]([Cl:20])[CH:19]=1)[NH:16][CH2:15][CH2:14][CH2:13]2)(O)=O.N[CH:24]1[CH2:29][CH:28]2[CH2:30][CH2:31][N:25]1[CH2:26][CH2:27]2.C([O-])([O-])=O.[K+].[K+].C(Cl)(Cl)Cl.CC[N:44](CC)CC>C(Cl)(Cl)Cl.O>[N:25]12[CH2:31][CH2:30][CH:28]([CH2:27][CH2:26]1)[CH:29]([NH:44][C:11]([C:10]1[C:2]([O:4][CH2:5][CH3:6])=[C:12]3[C:17](=[C:18]([Cl:20])[CH:19]=1)[NH:16][CH2:15][CH2:14][CH2:13]3)=[O:21])[CH2:24]2

Participants

8

Reactant 5

HCID 10928Ethyl chloroformateHCID 11430Potassium CarbonateHCID 148832326-Carboxy-8-chloro-5-methoxy-1,2,3,4-tetrahydroquinolineHCID 189269681-Azabicyclo[2.2.2]octan-2-amineHCID 18929042Triethylamine chloroform

Product 1

HCID 19989917(N-1-azabicyclo[2.2.2]oct-3-yl)-8-chloro-5-ethoxy-1,2,3,4-tetrahydroquinoline-6-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Conditions

Temperature
-20 °C

Procedure

Ethyl chloroformate (25 ml) is added to a stirred mixture of the acid compound of step 6 above (0.7 g) in CHCl3 -Et3N (25 ml/0.8 g) chilled to -20° C. and stirring is continued for 20 min. Aminoquinuclidine (3.1 g) and a saturated aqueous K2CO3 solution (6 ml) are added to the reaction mixture. Stirring is continued for 30 minutes while slowly warning to RT. The mixture is diluted with CHCl3 and H2O, stirred for 5 minutes and the aqueous layer was separated. The organic layer is washed with H2O, dried (MgSO4) and evaporated affording a foamy solid which is chromatographed on silica and converted to the hygroscopic hydrochloride salt of the desired product, M.P. 160° C. Elemental Analysis: Calc'd C 55.96, H 6.52, N 10.88; Calc'd(as Hydrate) C 53.47, H 6.73, N 10.39; Found C 53.45, H 7.34, N 10.26. The dihydrochloride salt has the same melting point and the following elemental analysis: Calc'd C 51.13, H 6.20, N 9.94; Found C 51.41, H 6.92, N 10.15.

Workup

  1. stirringStirring
  2. waitis continued for 30 minutes
  3. customwhile slowly warning to RT
  4. stirringstirred for 5 minutes
  5. customthe aqueous layer was separated
  6. washThe organic layer is washed with H2O
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customaffording a foamy solid which
  10. customis chromatographed on silica

Sources & evidence

ORD record
ord-3b0637889f044d4ea4555fe921f5e877
Source dataset
uspto-grants-1990_04
Patent number
US04920219

Reaction notes

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